Recent Advances in Our Understanding of Insulin Action and Insulin Resistance

Insulin signaling at the target tissue results in a large array of biological outcomes. These events are essential for normal growth and development and for normal homeostasis of glucose, fat, and protein metabolism. Elucidating the intracellular events after activation of the IR has been the primary focus of a large number of investigators for decades, and for excellent reasons. Understanding the signaling pathways involved in insulin action could lead to a better understanding of the pathophysiology of insulin resistance associated with obesity and type 2 diabetes, and identifying key molecules and processes could lead to newer and more effective therapeutic agents for treating these common disorders. This review summarizes our previous understanding of how insulin acts and outlines some recent developments in our understanding of insulin action and insulin resistance at the cellular level, beginning with a discussion on the discovery of evolutionarily conserved molecules of the insulin signaling pathways. This article will also provide a summary of a few in vitro and cellular models of insulin resistance and a description of some new paradigms in the cellular mechanisms of insulin action. This review will not attempt to be all-inclusive; for a more comprehensive understanding, readers are referred to more complete reviews on insulin action (1–5).